Certain 1,1 - dihydroperfluoroalkylpyridinium trifluoromethane sulfonates



United States Patent 3,488,358 CERTAIN 1,1 DIHYDROPERFLUOROALKYL- PYRIDINIUM TRIFLUOROMETHANE SUL- FONATES Jerry E. Robertson, North Oaks, Minn., assignor to Minnesota Mining and Manufacturing Company, St. Paul, Minn., a corporation of Delaware No Drawing. Filed Mar. 6, 1967, Ser. No. 620,665 Int. Cl. C07d 31/26, 31/48 U.S. Cl. 260-2943 2 Claims ABSTRACT OF THE DISCLOSURE Certain fluorocarbon quaternary salts, a process for their preparation and compositions containing thesalts are disclosed. These salts are shown to have antimicrobial properties.

BRIEF SUMMARY OF THE INVENTION This invention relates to antimicrobial (e.g. antibacterial and antifungal) substances and to compositions containing them. More particularly, it relates to fluorocarbon quaternary salts and compositions thereof.

Various quaternary salts are known to be useful and active antimicrobials. Certain fluorocarbon quaternary salts have also been known previously e.g., (see U.S. Patents 2,727,923, 2,759,019, 2,764,602 and 2,764,603). These have been shown to be surface active compounds with unusual properties, but their use as antimicrobials has not been disclosed. Indeed, the fluorocarbon quaternary salts, particularly those with larger fluorocarbon groups (e.g. above C F would be expected to have little or no antimicrobial activity since such fluorocarbon groups normally reduce or obviate pharmaceutical activity. The present invention relates to a novel class of fluorocarbon quaternary salts (containing relatively large fluorocarbon groups) which are not only unexpectedly active antimicrobials, but which, as will be shown, are much safer for certain applications than previously known quaternary antimicrobials.

It is an object of the present invention to provide a novel class of quaternary compounds.

It is another object of the present invention to provide novel antimicrobial compositions comprising certain new fluorocarbon quaternary compounds in a pharmaceutical medium.

It is another object of the invention to provide a new method of combatting microbes comprising contracting them with a fluorocarbon quaternary compound.

Still other objects of the invention will become apparent to those skilled in the art from the following detailed description.

DETAILED DESCRIPTION In accordance with the various aims and concepts of the present invention, there are provided fluorocarbon substituted quaternary compounds of the formula:

wherein m is 5-7. These compounds are conveniently prepared by treating pyridine with an alkylating agent, such as in an inert solvent, usually at an elevated temperature.

The high degree of safety of the compounds of the invention as antimicrobials is of major importance in various areas of use. An example of this is topical application to wounds of domestic animals or pets. Since the wounded area is likely to be licked 'by the animal, it is important that the antimicrobial be as non-toxic as possible while 3,488,358 Patented Jan. 6, 1970 ice still retaining its effectiveness. Another area in which safeness is important is in oral antiseptics such as mouth washes.

The relative safety of compounds for therapeutic uses is commonly measured as a Therapeutic Index, i.e. the ratio of effectiveness to lethality. In the present case, this can be measured as the ratio of the effectiveness against microorganisms to the lethality against test animals.

As antimicrobial agents, the compounds of this invention may be applied directly and alone to the tissue or material to be treated or conventional carriers or diluents may be incorporated with them before application. The choice of carrier or diluent and the concentration of the active ingredient are determined by the use of the composition.

For treatment of topical infections in mammals, e.g. in dogs or other domestic animals, the compositions are usefully employed as ointments which are not readily removed from the treated area by movement or rubbing. Other pharmaceutical carriers which can be used are organic solvents (such as alcohols, e.g. ethyl alcohol), Water (to dissolve or suspend the active ingredient), solid inert materials such as talc, bentonite, kieselguhr, diatomaceous earth, and the like, emulsifying agents, etc. The fluorocarbon quaternary salts of the invention can also be dispersed in pressure sensitive adhesives for use in surgical tapes, drapes, etc. In such cases, the adhesives can also be considered to be pharmaceutical extending media.

The following will illustrate the preparation of the compositions of the invention and their antimicrobial effectiveness.

1,1 dihydroperfluorooctyl trifluoromethanesulfonate (5.3 g., 0.010 mole) was added dropwise to a stirred solution of 1.8 g. (0.022 mole) of pyridine in ml. 2-butanone at reflux temperature. After heating for an additional two days, the mixture was concentrated to dryness. The oily residue was triturated with ether to .aiford a solid which was collected and recrystallized twice from chloroform to afford 1.4 g. (23%) of N-(1,1-dihydroperfluorooctyl)pyridinium trifluoromethanesulfonate having the structure:

e C) )v-ormormomcmsm The melting point of this compound was -1115 and the results of analytical tests thereon were as follows:

Calcd for C13H7F15NCF3O3S: C, 27.5; H, 1.5. Found: C, 27.6; H, 1.3.

The 1.1 dihydroperfluorooctyl trifluoromethanesulfonate used in the foregoing preparation was prepared according to the method described by Hensen (J. Org. Chem, vol. 30, p. 4322, 1965) utilizing 1,1-dihydroperfluorooctyl alcohol.

The effectiveness of the perfluorooctyl pyridinium salt as an antimicrobial was evaluated against four bacteria (Staphylococcus aureus, Streptococcus sp. 104 Escherichio coli and Bacillus subtilis) and two fungi (Aspcrgillus niger and Candida albicans) using a variation of the agar plate diffusion method of Vincent and Vincent (Proc. Soc. Expty. Biol. Med. 55: 162-164) using culture media based on the synthetic glucose-salts medium of Davis and Mingioli (Jour. Bact. 66: 129-136). Both serum free cultures and cultures with serum or blood were tested with each microorganism. For purposes of comparison an identical set of tests were run utilizing the well known and highly active antimicrobial compound cetyl pyridinium chloride (ref. The Merck Index of Chemicals and Drugs, Published by Merck and Co., Inc.-, Rahway, N.J., Seventh Edition, 1960, p. 227). The perfluorooctyl pyridinium salt was found to be significantly more active against the bacteria than the cetylpyridinium chloride and slightly less active against the fungi.

Comparing the same two compounds as to their acute 2. A compound according to claim 1 wherein m is 6.

:oxicity in rate it was found that the LD (oral) of the perfluorooctyl pyridinium salt is 1159 mg./kg. and that References Cited he LD (oral) of the cetylpyridinum chloride it 538 FOREIGN PATENTS ng./kg. Thus the efl'ective safety (Therapeutic Index) 5 of the perfluorooctyl pyridinium salt is very significantly 1,059,278 2/1907 Great Brltalllgreater than that of the cetylpyridinium chloride against 90th bacterial and fungi, particularly the former. HENRY JI ES, Primary Examiner What is claimed is: 1. A quaternary compound of the formula: 10 Asslstant Exammer O Il-CH (CF -OF, CF3SO3 US. Cl. X.R. A 424263 wherein m is 5-7. 

